dbSNP rs3754112: CD101:p.Asn225Ser (chr1-117011799-A-G) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001256106.3(CD101):c.674A>G(p.Asn225Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.287 in 1,613,850 control chromosomes in the GnomAD database, including 71,147 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.23 ( 4988 hom., cov: 32)

Exomes 𝑓: 0.29 ( 66159 hom. )

Consequence

CD101
NM_001256106.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.905

Publications

38 publications found

Variant links:

Genes affected

CD101 (HGNC:5949): (CD101 molecule) Predicted to enable hydrolase activity, acting on carbon-nitrogen (but not peptide) bonds, in cyclic amides. Predicted to be involved in cell surface receptor signaling pathway. Predicted to act upstream of or within positive regulation of myeloid leukocyte differentiation. Located in extracellular exosome. [provided by Alliance of Genome Resources, Apr 2022]

CD101 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0013926327).

BP6

Variant 1-117011799-A-G is Benign according to our data. Variant chr1-117011799-A-G is described in ClinVar as Benign. ClinVar VariationId is 1280460.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.317 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CD101	NM_001256106.3 link	c.674A>G	p.Asn225Ser	missense_variant	Exon 3 of 10	ENST00000682167.1	NP_001243035.1	Q93033

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CD101	ENST00000682167.1 link	c.674A>G	p.Asn225Ser	missense_variant	Exon 3 of 10		NM_001256106.3	ENSP00000508039.1	Q93033
CD101	ENST00000369470.1 link	c.674A>G	p.Asn225Ser	missense_variant	Exon 3 of 10	1		ENSP00000358482.1	Q93033
CD101	ENST00000256652.8 link	c.674A>G	p.Asn225Ser	missense_variant	Exon 3 of 9	2		ENSP00000256652.4	Q93033

Frequencies

GnomAD3 genomes

AF:

0.230

AC:

35033

AN:

152012

Hom.:

4988

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0802

Gnomad AMI

AF:

0.173

Gnomad AMR

AF:

0.222

Gnomad ASJ

AF:

0.437

Gnomad EAS

AF:

0.0697

Gnomad SAS

AF:

0.171

Gnomad FIN

AF:

0.290

Gnomad MID

AF:

0.278

Gnomad NFE

AF:

0.320

Gnomad OTH

AF:

0.258

GnomAD2 exomes

AF:

0.249

AC:

62534

AN:

250790

AF XY:

0.255

show subpopulations

Gnomad AFR exome

AF:

0.0704

Gnomad AMR exome

AF:

0.160

Gnomad ASJ exome

AF:

0.435

Gnomad EAS exome

AF:

0.0760

Gnomad FIN exome

AF:

0.292

Gnomad NFE exome

AF:

0.323

Gnomad OTH exome

AF:

0.290

GnomAD4 exome

AF:

0.293

AC:

427730

AN:

1461720

Hom.:

66159

Cov.:

AF XY:

0.291

AC XY:

211668

AN XY:

727156

show subpopulations

African (AFR)

AF:

0.0702

AC:

2349

AN:

33476

American (AMR)

AF:

0.168

AC:

7498

AN:

44710

Ashkenazi Jewish (ASJ)

AF:

0.436

AC:

11385

AN:

26136

East Asian (EAS)

AF:

0.0812

AC:

3222

AN:

39692

South Asian (SAS)

AF:

0.180

AC:

15549

AN:

86248

European-Finnish (FIN)

AF:

0.292

AC:

15577

AN:

53412

Middle Eastern (MID)

AF:

0.286

AC:

1648

AN:

5768

European-Non Finnish (NFE)

AF:

0.318

AC:

353831

AN:

1111886

Other (OTH)

AF:

0.276

AC:

16671

AN:

60392

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.478

Heterozygous variant carriers

17175

34351

51526

68702

85877

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

11152

22304

33456

44608

55760

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.230

AC:

35020

AN:

152130

Hom.:

4988

Cov.:

AF XY:

0.226

AC XY:

16790

AN XY:

74380

show subpopulations

African (AFR)

AF:

0.0799

AC:

3317

AN:

41518

American (AMR)

AF:

0.222

AC:

3387

AN:

15288

Ashkenazi Jewish (ASJ)

AF:

0.437

AC:

1515

AN:

3466

East Asian (EAS)

AF:

0.0698

AC:

361

AN:

5170

South Asian (SAS)

AF:

0.172

AC:

828

AN:

4814

European-Finnish (FIN)

AF:

0.290

AC:

3068

AN:

10580

Middle Eastern (MID)

AF:

0.265

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.320

AC:

21770

AN:

67980

Other (OTH)

AF:

0.255

AC:

539

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1304

2608

3912

5216

6520

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

370

740

1110

1480

1850

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.293

Hom.:

20414

Bravo

AF:

0.221

TwinsUK

AF:

0.315

AC:

1169

ALSPAC

AF:

0.306

AC:

1178

ESP6500AA

AF:

0.0890

AC:

392

ESP6500EA

AF:

0.325

AC:

2794

ExAC

AF:

0.248

AC:

30141

EpiCase

AF:

0.325

EpiControl

AF:

0.326

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Feb 23, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is associated with the following publications: (PMID: 29108000) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.73

BayesDel_noAF

Benign

-0.68

CADD

Benign

0.30

(source)

DANN

Benign

0.83

DEOGEN2

Benign

0.13

T;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.0

FATHMM_MKL

Uncertain

0.84

LIST_S2

Benign

0.64

T;.

MetaRNN

Benign

0.0014

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

-0.38

N;N

PhyloP100

0.91

PrimateAI

Benign

0.23

PROVEAN

Benign

-1.0

N;N

REVEL

Benign

0.059

Sift

Benign

0.054

T;T

Sift4G

Benign

0.099

T;T

Polyphen

0.0

B;B

Vest4

0.012

MPC

0.075

ClinPred

0.0074

GERP RS

-2.3

Varity_R

0.045

gMVP

0.079

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over